Many different types of chemical compounds have been used in the past to treat tumors in mammals including humans. Examples of such compounds are the nitrogen mustards, estrogen, insulin, tolbutamide, hydrazine sulfate, fluorouracil and the biguanides. The exact mode of action encountered in such chemotherapy has never been firmly established and the degree of successful therapy has been nominal at best.
During the past 4 decades, it has been generally recognized that carbohydrate metabolism in the neoplastic process has some relationship to cancerous growths, but its exact role has not been clearly defined. It is now proposed that in cancer subjects, gluconeogenesis together with glycolysis constitutes a type of metabolic circuit whereby the body is depleted of energy reserves, resulting in cachexia, the latter being the process of gradual bodily deterioration and weight loss in the presence of a flourishing tumor. The process of cachexia is dependent on the free functioning of the metabolic pathways of gluconeogenesis in which energy from normal cells is expended upon gluconeogenic precursors (compounds containing 2-5 carbon atoms) in their synthesis to glucose (6 carbon atoms). A more detailed explanation of the carbohydrate mechanisms which are operative in such metabolism will be hereinafter more fully discussed. At this point, it is sufficient to state that if the process of gluconeogenesis can be inhibited, and preferably without interfering with other normal metabolic processes, including glycolysis, a marked reduction in energy expended or drained from normal body cells would take place, leading to an inhibition of cachexia; and at the same time a resulting decrease or reduction in the tumor growth rate. It has been found that under abnormal conditions large amounts of glucose can be synthesized via gluconeogenesis in amounts far in excess of the total minimum daily body requirement for glucose. The resulting energy drawn from normal tissues caused by such a great augmentation in gluconeogenesis (such as the recycling of lactic acid to glucose) can be tremendous, utilizing the equivalent of at least six molecules of adenosine triphosphate (ATP) per new glucose molecule formed.